Colorectal Cancer Metastases Settle in the Hepatic Microenvironment Through [alpha]5[beta]1 Integrin

• Published in: Journal of cellular biochemistry 2015-10, Vol.116 (10), p.2385
• Main Authors: Pelillo, Chiara, Bergamo, Alberta, Mollica, Hilaria, Bestagno, Marco, Sava, Gianni
• Format: Article
• Language: English
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.25189

Colorectal cancer (CRC) metastasis dissemination to secondary sites represents the critical point for the patient's survival. The microenvironment is crucial to cancer progression, influencing tumour cell behaviour by modulating the expression and activation of molecules such as integrins, the cell-extracellular matrix interacting proteins participating in different steps of the tumour metastatic process. In this work, we investigated the role of [alpha]5[beta]1 integrin and how the microenvironment influences this adhesion molecule, in a model of colon cancer progression to the liver. The culture medium conditioned by the IHH hepatic cell line, and the extracellular matrix (ECM) proteins, modulate the activation of [alpha]5[beta]1 integrin in the colon cancer cell line HCT-116, and drives FAK phosphorylation during the process of cell adhesion to fibronectin, one of the main components of liver ECM. In these conditions, [alpha]5[beta]1 modulates the expression/activity of another integrin, [alpha]2[beta]1, involved in the cell adhesion to collagen I. These results suggest that [alpha]5[beta]1 integrin holds a leading role in HCT-116 colorectal cancer cells adhesion to the ECM through the modulation of the intracellular focal adhesion kinase FAK and the [alpha]2[beta]1 integrin activity. The driving role of the tumour microenvironment on CRC dissemination, here detected, and described, strengthens and adds new value to the concept that [alpha]5[beta]1 integrin can be an appropriate and relevant therapeutic target for the control of CRC metastases. J. Cell. Biochem. 116: 2385-2396, 2015. © 2015 Wiley Periodicals, Inc.